A Trial of Palliative Chemotherapy, Radiation and Immune Treatment for Oesophageal Cancer: PALEO Study

NCT06290505 | Recruiting Phase 2 DMC

• 1 other identifier: PALEO
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to investigate the effects of the addition of the stereotactic body radiotherapy and durvalumab to a well tolerated 2 week chemotherapy and radiation treatment regimen in people with esophageal cancer that is locally advanced or has spread to another area of the body (metastasized).

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival rate is the proportion of patients alive and progression free (the cancer has not worsened) assessed by CT scan and clinical review.

  The interval from the date of participant registration to the date of a progression free survival event: 1. date of the first CT scan to show disease progression 2. patient is judged to have progressed by the responsible investigator (in the event that no RECIST assessment is available) 3. death occurs.

  6 months

Secondary Outcomes (8)

• Duration of dysphagia relief

  Mellow score will be assessed at days 1, 8, 15, 29, 43, 57 and then every 4 weeks thereafter until the end of treatment visits (30days after the last dose).

• Nutritional status

  To be administered by a qualified dietician from date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 weeks.

• Quality of life change using the - European organisation for the research and treatment of cancer quality of life questionnaire QLQ-C30

  Through study completion, an average of 1 year, using the 4-point ordinal scale - not at all, a little, quite a bit and very much

• Quality of life change using the - European organisation for the research and treatment of cancer quality of life questionnaire QLQ-OES18

  Through study completion, an average of 1 year, using the 4-point ordinal scale - not at all, a little, quite a bit and very much

• Response rate in metastatic lesions

  Assessment with imaging scans is performed at baseline then every 6 weeks while in treatment, then every 12 weeks until disease progression or date of death from any cause, whichever came first, assessed up to 96 weeks.

Study Arms (1)

Treatment

EXPERIMENTAL

Participants will receive 2 weeks of therapy with concurrent hypofractionated radiotherapy (30Gy/10#), weekly carboplatin (AUC2), weekly paclitaxel (50mg/m2) and durvalumab (1500mg) intravenously every 4 weeks, followed by durvalumab monotherapy continuing at 1500mg intravenously every 4 weeks until disease progression or 24 months of therapy. One to five metastases will be treated with stereotactic radiotherapy (24Gy/3#) 4 weeks after the completion of the chemoradiotherapy to the primary tumour. Monitoring of adherence to treatment will be done by attendance at booked appointments

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab will be supplied by AstraZeneca as a 500 mg vial concentrate for solution for infusion. The solution contains 50 mg/mL durvalumab, 26 mM histidine/histidine-hydrochloride, 275 mM trehalose dihydrate, and 0.02% weight/volume (w/v) polysorbate 80; it has a pH of 6.0 and density of 1.054 g/mL. The label-claim volume is 10 mL. Durvalumab is a sterile, clear to opalescent, colorless to slightly yellow solution, free from visible particles. Investigational product vials are stored at 2°C to 8°C and must not be frozen. Investigational product must be kept in original packaging until use to prevent prolonged light exposure.

Also known as: Imfinzi

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females \> 18 years of age.
• Biopsy proven adenocarcinoma or squamous cell carcinoma of the esophagus or gastro-oesophageal junction
• Oligometastatic disease (1-5 lesions outside the primary tumour radiotherapy field on FDG-PET scan), or locoregionally advanced disease unsuitable for either surgical resection or radical chemoradiotherapy
• Symptomatic dysphagia (Mellow score greater than 0)
• ECOG performance status 0-2
• Anticipated life expectancy of greater than 12 weeks.
• Body weight of greater than 30kg.
• Adequate bone marrow function, with values within the ranges specified below. Blood transfusions are permissible.
• White blood cell count greater than or equal to 2 x (10 to the power of 9)/L
• Absolute neutrophil count greater than or equal to 1.5 x (10 to the power of 9)/L
• Platelets greater than or equal to 100 x (10 to the power of 9)/L
• Haemoglobin greater than or equal to 90g/L
• Adequate liver function, with values within the ranges specified below:
• Alanine transferase less than or equal to 2.5 x upper limit of normal (ULN)
• Aspartate transferase less than or equal to 2.5 x ULN

You may not qualify if:

• Bulky or organ-threatening metastatic disease requiring upfront higher dose chemotherapy in the judgement of the treating clinician.
• Known tumour HER2 positivity (IHC 2+ or more and HER2 gene amplification on in situ hybridisation) if oligometastatic disease.
• Previous systemic therapy for oesophageal or GOJ carcinoma.
• Previous thoracic radiotherapy. Prior palliative radiotherapy to bony metastases is permitted.
• Esophageal stent in situ.
• Known tracheo-oesophageal fistula.
• Known leptomeningeal or brain metastases.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to first day of study treatment. Note: Local surgery of isolated lesions for palliative intent is permitted.
• History of another malignancy within the last 3 years, with the exception of adequately treated non-melanomatous skin cancer, carcinoma in situ and superficial transitional cell carcinoma of the bladder.
• Prior therapy with an anti-PD1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• Sensory neuropathy of grade 2 or higher severity per CTCAE v5.0.
• History of allergy or hypersensitivity to study drug components, or other contraindications to any of the study drugs. Active or prior documented autoimmune disorders (including inflammatory bowel disease \[e.g., ulcerative colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). Patients with the following conditions are exceptions to this criterion:
• Vitiligo or alopecia.
• Hypothyroidism (e.g., following Hashimoto syndrome) stable on thyroid hormone replacement.
• Any chronic skin condition (e.g. psoriasis) that does not require systemic therapy.

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead

Study Sites (9)

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

RECRUITING

Border Medical Oncology

Albury, New South Wales, 2640, Australia

ACTIVE NOT RECRUITING

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, Australia

RECRUITING

St Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

Auckland Hospital

Grafton, Auckland, 1023, New Zealand

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Fiona Day, Dr

  Calvary Mater Newcastle

  STUDY CHAIR

• Jared Martin, Professor

  Calvary Mater Newcastle

  STUDY CHAIR

Central Study Contacts

Sandra Bahamad

CONTACT

02 7208 2714; sandra@gicancer.org.au

Sukanya Sathyamurthie

CONTACT

02 7208 2719; Sukanya@gicancer.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: March 4, 2024
• Study Start: December 8, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2029
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (8); NZ (1)